Adding Value During Biosimilar Development – Interactions with a CRO Case Study
Enabling Critical Data-driven Decisions
mAbxience is a Spanish biotech company, specializing in the research, development, manufacture and commercialization of biosimilar drugs with manufacturing sites in Leon, Spain and Buenos Aires, Argentina. Founded in 2009 and part of the Spanish multinational CHEMO Group, mAbxience is committed to bringing high-quality biosimilar products to the global market. mAbxience currently has two biosimilars on the market, Novex® (rituximab) and Bevax® (bevacizumab), with a further 4 biosimilars in its pipeline, at different development stages.
The Need for Speed
Biosimilars are an attractive market to many biotech companies, as they offer significant time and cost savings when compared to the development of a new biological entity (NBE). To demonstrate biosimilarity, it is essential that the biological product has been proven to be highly similar to the originator product and has no clinically meaningful differences in terms of its safety, and efficacy. An abbreviated licensure pathway for products which are able to demonstrate this has been outlined by the EMA, FDA & WHO¹. The foundation for approval is based on a robust analytical package that demonstrates similarities between the reference and biosimilar product.
Biosimilar development requires the implementation of sensitive, accurate analytical methods at an early stage in order to support candidate selection and subsequent process development. A totality of evidence and step-wise orthogonal approach is recommended by regulators to support a claim of biosimilarity.
“The biosimilar market is highly competitive and mAbxience are not the only company developing biosimilars. It is therefore important to be on time to market with biosimilars whilst maintaining your product quality and being aware of the cost of goods of manufacture.” – Annette Beattie, CMC Specialist, mAbxience.
To adhere to the aggressive timelines of biosimilar development and the need for increased analytical analysis, mAbxience sought additional analytical support by partnering with an analytical CRO who could provide analytical data quickly, whilst not compromising on service or data quality.
mAbxience selected Sartorius Stedim BioOutsource as their analytical CRO partner, as they offered a range of pre-qualified, off-the-shelf assays, which enabled them to obtain analytical data quickly for 3 of their molecules in development: rituximab, bevacizumab, and adalimumab.
“BioOutsource had available off-the-shelf methods for us to obtain analytical data quickly and also use the same analytical methods to choose and select the best clones for development.” – Annette Beattie, CMC Specialist, mAbxience.
These assays are a great starting point but can be further optimized for client specific objectives such as, tracking assay performance over time, increasing sample throughput to reduce variation/timelines or analyzing and presenting data in client specific formats.
In addition, Sartorius Stedim BioOutsource provided additional efficiencies through their client management model. mAbxience has a dedicated client manager who serves as a single point of contact and who is responsible for bringing together an internal project team to ensure testing slots are scheduled to meet project deadlines, technical queries are addressed by the most appropriate personnel and that the project timelines are adhered to. This model meant Sartorius Stedim BioOutsource were ideally placed to support 2 large and high priority mAbxience biosimilar development programs at the same time as multiple biosafety testing projects.
Technical Expertize Adds Value
For mAbxience, the first step is to characterize and understand the reference product. Sartorius Stedim BioOutsource applied their extensive expertize and knowledge to quickly and effectively characterize the functional and binding activity of mAbxience’s reference products using various assay methods:
The deep understanding and technical knowledge within the team at Sartorius Stedim BioOutsource meant that they could assist and include independent control samples into the assessments which allowed mAbxience to confidently compare data between similarity studies throughout the course of the development programme.
Very early in the collaboration mAbxience recognized the need for additional controls in each assay to ensure consistency of data generated over a wide time period. By utilizing Sartorius Stedim BioOutsource’s expertize suitable assays were developed. The close interaction and support lead to improved assay design to give an inter assay precision level of <15%CV and at the same time meeting the objective of inter assay consistency. This not only improved assay control, it enabled mAbxience to have confidence in the consistency of reported results from early characterization studies through process optimization steps and onto subsequent process robustness studies. Further consideration could be given to assay validation for subsequent clinical and commercial GMP lot release.
“Improving control, and gaining confidence in the reported results from our analytical assessments, would not have been possible without support from the technical team at BioOutsource.” – Annette Beattie, CMC Specialist, mAbxience.
The readily available assays allowed mAbxience to quickly obtain analytical data, which supported their biosimilar development timelines. The assistance and guidance from the technical team at Sartorius Stedim BioOutsource enabled further development of assays to meet mAbxience’s specific requirements. Moreover, mAbxience has been able to improve assay performance and control as the programme moved through the development life-cycle and has confidence in the results to support fingerprint-like similarity.
“The interaction with BioOutsource has made us able to target those analytical methods so that we get a much improved method, a much more precise method that really allows us to strongly defend our claim to fingerprint like similarity.” – Annette Beattie, CMC Specialist, mAbxience.
For more information on mAbxience please visit: www.mabxience.com
EMA: European Medicines Agency
FDA: Food and Drug Administration
WHO: World Health Organization